Analysis Showed Teriparatide Reduced Fracture Risk Independent of Bone Turnover
05 October 2004 - 12:00PM
PR Newswire (US)
Analysis Showed Teriparatide Reduced Fracture Risk Independent of
Bone Turnover SEATTLE, Wash., Oct. 4 /PRNewswire-FirstCall/ -- Data
presented today at the 26th annual meeting of the American Society
for Bone and Mineral Research (ASBMR) show that the ability of
teriparatide to prevent fractures remained consistent regardless of
pretreatment bone turnover status. Bone is living tissue that
constantly regenerates itself by breaking down and reforming, a
process referred to as bone turnover. Osteoporosis can occur when
bone break down exceeds bone formation. "In most cases, rapid bone
turnover can be dangerous and lead to fracture in osteoporotic
patients," said the study's primary investigator, Pierre Delmas,
MD, Claude Bernard University of Lyon, France. "In this study,
regardless of whether patients had high turnover rates before being
treated, we saw a reduced risk of fractures with teriparatide."
This post-hoc analysis examined biochemical markers of bone
turnover, which provide information about the rate of bone
turnover. This rate can vary considerably in postmenopausal women
with osteoporosis. In this study, the impact of the pretreatment
bone turnover rate on the response to teriparatide was examined.
FORTEO(R) (teriparatide [rDNA origin] injection), the first and
only bone formation agent approved for the treatment of
osteoporosis, was granted FDA approval in November 2002. It
stimulates new bone formation by increasing the number and activity
of bone forming cells called osteoblasts. FORTEO is approved for
the treatment of osteoporosis in postmenopausal women who are at
high risk for fracture and to increase bone mass in men with
primary or hypogonadal osteoporosis who are at high risk for
fracture. These include men (and postmenopausal women) with a
history of osteoporosis-related fracture, or who have multiple risk
factors for fracture, or who have failed or are intolerant to
previous osteoporosis therapy, based upon physician assessment.
Until FORTEO's approval, the only approved osteoporosis treatments
were antiresorptives, which work mainly to slow or stop bone loss
by reducing the number and action of bone-removing cells called
osteoclasts. About the Analysis To determine whether rate of bone
turnover affects teriparatide's effect, this analysis looked at the
relationship between baseline biochemical markers of bone turnover
and the ability of teriparatide to reduce the occurrence of
fractures. Five biochemical markers from postmenopausal women with
osteoporosis who participated in the pivotal FORTEO Fracture
Prevention Trial were analyzed. The Fracture Prevention Trial
(FPT), a registration trial for FORTEO, was a randomized,
double-blinded, placebo controlled study that enrolled 1,637 women
with osteoporosis. Subjects were randomized to teriparatide 20
mcg/day (marketed as FORTEO), teriparatide 40 mcg/day or placebo
for a median of 19 months. A subset of 520 women had biochemical
markers of bone turnover (serum bone-specific alkaline phosphatase
[BSAP], serum carboxy-terminal extension peptide of procollagen
type 1 [PICP], urinary N-terminal telopeptide [NTX], and urinary
free deoxypyridinoline [DPD]) measured at baseline. A partially
overlapping subset of 771 women also had serum amino-terminal
extension of peptide of procollagen type 1 [PINP] evaluated at
baseline. BSAP, PICP and PINP are all markers of bone formation,
whereas DPD and NTX are markers of bone resorption. Analysis found
that subjects with higher baseline concentrations of BSAP, PINP,
NTX and DPD had a higher risk of a new fragility fracture.
Teriparatide significantly reduced the risk of vertebral and
nonvertebral fragility fractures regardless of pretreatment bone
turnover, according to study results. Important Safety Information
about FORTEO In two-year studies in rats, teriparatide caused an
increase in the incidence of osteosarcoma, a malignant bone tumor,
which was dependent on dose and duration of treatment. Although no
case of osteosarcoma has been reported in the patients who received
FORTEO in clinical trials, it is not known if humans treated with
FORTEO are at increased risk for this cancer. FORTEO should be
prescribed only to patients for whom the potential benefits are
considered to outweigh the potential risk. The drug should not be
prescribed for patients at increased baseline risk for
osteosarcoma, including patients with Paget's disease of bone or
unexplained elevations of alkaline phosphatase, children or growing
adults, or those who have had prior external beam or implant
radiation therapy involving the skeleton. Additionally, patients
with bone metastases or a history of skeletal malignancies, and
those with metabolic bone diseases other than osteoporosis, should
not receive FORTEO. Patients with high levels of calcium in their
blood should not receive FORTEO due to the possibility of
increasing their blood levels of calcium. In clinical trials, the
most frequent treatment-related adverse events reported at the
20-microgram (mcg) dose approved for marketing were mild, similar
to placebo and generally did not require discontinuation of
therapy. Reported adverse events that appeared to be increased by
FORTEO treatment were leg cramps and dizziness (2.6 and 8 percent,
respectively), compared with placebo (1.3 percent and 5.4 percent,
respectively). FORTEO is supplied in a disposable pen device that
can be used for up to 28 days to give once-daily self-administered
injections. FORTEO is available in a 20-mcg dose and should be
taken for a period of up to 24 months. Lilly has implemented a risk
management program that includes comprehensive measures regarding
the appropriate use of FORTEO in the target patient population. A
Medication Guide explaining the details of the drug to the patient
also accompanies the product. FORTEO also has a black box warning
in its package insert about the osteosarcoma findings in rats
during preclinical testing. For full prescribing information,
please visit http://www.forteo.com/ . About Osteoporosis More than
50 percent of all women over the age of 75 are estimated to have
osteoporosis, and due to their advanced age, have a high risk of
fracture. In fact, most American women over the age of 50 will
experience one or more osteoporosis-related fractures during their
lifetimes, and women with osteoporosis who have two or more
previous fractures have up to a nine times greater risk of future
fracture compared with women who have not suffered a previous
fracture. About Lilly Lilly, a leading innovation-driven
corporation is developing a growing portfolio of first-in-class and
best-in-class pharmaceutical products by applying the latest
research from its own worldwide laboratories and from
collaborations with eminent scientific organizations. Headquartered
in Indianapolis, Ind., Lilly provides answers -- through medicines
and information -- for some of the world's most urgent medical
needs. Additional information about Lilly is available at
http://www.lilly.com/ . (Logo:
http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO )
http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO DATASOURCE:
Eli Lilly and Company CONTACT: Keri S. McGrath of Eli Lilly and
Company, Cell: +1-317-457-5613, Office: +1-317-651-6001, Email:
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